Independent Studies of Dextromethorphan and of Donepezil Hydrochloride for Rett Syndrome
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|ClinicalTrials.gov Identifier: NCT00069550|
Recruitment Status : Unknown
Verified December 2004 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
Recruitment status was: Recruiting
First Posted : September 30, 2003
Last Update Posted : June 24, 2005
|Condition or disease||Intervention/treatment||Phase|
|Rett Syndrome||Drug: dextromethorphan Drug: donepezil hydrochloride||Phase 3|
RTT is a neurodevelopmental disorder characterized by apparently normal early development followed by loss of purposeful hand use, distinctive hand stereotypies, slowed brain growth, loss of language, respiratory irregularities, GI disturbances, gait abnormalities, seizures, and mental retardation. These symptoms appear between ages 6 and 18 months (stage 2 of the disease) following apparently normal development (stage 1). Subsequently, there is gradual stabilization of severe mental retardation and motor compromise (stage 3). The majority (70% to 80%) of patients demonstrate mutations in the methyl-CpG-binding-protein-2 (MeCP2) gene, a transcription repressor located on chromosome Xq28. The disorder predominantly affects females, but a few males with mutations in MeCP2 have been identified, even though many of them do not have the classic symptoms recognized in females.
Recent studies demonstrate increased brain N-methyl-D-aspartate (NMDA) receptors in stages 2 and 3 of the disease. This age-specific increase in glutamate levels and their receptors contribute to brain damage. This first study will examine the effectiveness of dextromethorphan, an NMDA receptor antagonist, to ameliorate symptoms. Participants will be randomized to receive one of three doses of dextromethorphan. All participants will be admitted to the hospital for three days at the beginning of the study. During the hospitalization, participants will undergo physical exam, Dexascan, MRI, EEG, behavioral assessment, laboratory testing, and neuropsychological evaluations. Six months after baseline assessment, participants will be rehospitalized for 3 days for similar assessments.
Reduction in choline acetyltransferase activity in RTT patients may also contribute to disturbed cortical development and psychomotor retardation in RTT. Therefore, the second part of the study will evaluate the effect of donepezil hydrochloride, an inhibitor of acetylcholine-esterase, on acetylcholine levels. This portion of the study will not begin until pharmacokinetic data for donepezil in children is available.
|Study Type :||Interventional (Clinical Trial)|
|Enrollment :||90 participants|
|Intervention Model:||Factorial Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pathogenesis of Rett Syndrome: Natural History and Treatment|
|Study Start Date :||September 2004|
|Study Completion Date :||June 2008|
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00069550
|Contact: SakkuBai R. Naidu, MD||443-923-2778|
|Contact: Barbara Ann Bradfordemail@example.com|
|United States, Maryland|
|Kennedy Krieger Institute||Recruiting|
|Baltimore, Maryland, United States|
|Contact: SakkuBai R. Naidu, MD 443-923-2778|
|Contact: Genila Bibat, MD 443-923-2778 firstname.lastname@example.org|
|Principal Investigator:||SakkuBai R. Naidu, MD||Hugo W. Moser Research Institute at Kennedy Krieger, Inc.|